Comparison of Isatuximab Administered as a Subcutaneous Injection or an Infusion as First-Line Treatment for Multiple Myeloma

Multiple myeloma is a cancer of the bone marrow in which certain immune cells, known as plasma cells, multiply uncontrollably. Plasma cells produce antibodies, which are important for fighting off infections in healthy individuals. The causes of the disease have not been definitively determined. Despite advances in treatment, the therapeutic approach is usually not aimed at a cure (curative), but rather at controlling symptoms and preventing the progression of the disease (palliative). The choice of treatment depends on various factors, such as the patient’s overall health, age, and disease activity. Treatment often involves a combination of immunomodulatory, targeted, and antibody-based medications, followed by high-dose chemotherapy with the reinfusion of the patient’s own stem cells, which were collected beforehand (autologous stem cell transplant). As initial treatment, multiple myeloma patients who are eligible for transplantation often receive what is known as induction therapy to reduce the disease burden before high-dose chemotherapy and subsequent stem cell transplantation. This typically involves a combination of lenalidomide (usually as a tablet), bortezomib (injected under the skin, subcutaneously), and the corticosteroid dexamethasone (usually as a tablet), as well as a CD38 antibody such as isatuximab (administered intravenously). The study drug isatuximab specifically targets the surface protein CD38, which is particularly abundant on myeloma cells. In this way, isatuximab helps the immune system recognize these cancer cells and destroy them selectively. In combination with lenalidomide, bortezomib, and dexamethasone, isatuximab is already approved as an intravenous therapy for the first-line treatment of newly diagnosed multiple myeloma patients who are eligible for stem cell transplantation. However, intravenous administration (as an infusion through a venous access site) often means longer treatment times for patients in a hospital or doctor’s office. A new, as yet unapproved form of isatuximab administration is subcutaneous injection—that is, an injection under the skin. Until now, isatuximab was the only drug in the combination therapy that had to be administered intravenously. Subcutaneous administration could make the therapy easier and less time-consuming for patients.

The goal of this Phase 3 study is to determine whether subcutaneous administration of isatuximab is just as effective as intravenous administration. To this end, patients will be randomly assigned to two study arms. In both groups, patients will receive induction therapy with isatuximab, lenalidomide, bortezomib, and dexamethasone. In the experimental arm of the study, isatuximab is administered subcutaneously via injection under the skin. In the comparison arm, isatuximab is administered as an intravenous infusion. In the study, the induction treatment consists of 3 cycles of 42 days each (18 weeks in total). In both arms, patients receive isatuximab on days 1, 8, 15, 22, and 29 of cycle 1, and on days 1, 15, and 29 of cycles 2 and 3. The study is open-label, meaning that both patients and medical staff know which treatment is being administered. The effectiveness of the treatment will be assessed 18 weeks after the start of treatment (following completion of induction therapy). Patients will be monitored as part of the study for up to 28 months after the start of the study.

Eligible participants are adults between the ages of 18 and 70 with newly diagnosed, previously untreated multiple myeloma who require systemic therapy. They must be suitable candidates for high-dose chemotherapy followed by autologous stem cell transplantation.